First, it demonstrates that investigational compounds in the mental health arena have a high bar of safety and efficacy to meet these days. This is true for drugs treating bipoloar, schizophrenia, depression and ADHD. That, in turn, means that (i) future treatments will be really, really proven safe and effective, or (ii) we will be in a holding pattern for a long time with the treatments we currently have because few will be able to jump the bar; or (iii) companies will be discouraged from this area of investigation at all. It may mean all three.

The letter from the FDA, about which the company was very forthcoming respecting content, outlines what the company must do if it wants to try to gain eventual approval on the compound. Note that the company states that the FDA admitted efficacy for iloperidone that was similar to an existing treatment, superior to placebo, but not superior to another comparator used in earlier trials, leading one to wonder how many comparators a company must use in the course of testing.

"The FDA stated that Vanda had demonstrated the effectiveness of iloperidone at 24 mg/day in the 3101 study for which the company reported results in December, 2006, and that the efficacy was similar to the active comparator, ziprasidone (Geodon(R), Pfizer Inc.). In addition, the FDA also stated that iloperidone was superior to placebo in patients with schizophrenia at doses of 12-16 mg/day and 20-24 mg/day in a prior study. However, the FDA expressed concern about the efficacy of iloperidone in patients with schizophrenia relative to the active comparator, risperidone (Risperdal(R), Johnson & Johnson), used in prior studies. The FDA indicated that it would require an additional trial comparing iloperidone to placebo and including an active comparator such as olanzapine (Zyprexa(R), Eli Lilly & Company) or risperidone in patients with schizophrenia to demonstrate the compound’s efficacy further. The FDA also stated that it would require Vanda to obtain additional safety data for patients at a dose range of 20 to 24 mg/day."

It strikes one that this is an example of what we may see in the Complete Response Letters to start flowing from CDER on August 11, so one of the interesting aspects of this letter is that it may be a glimpse of what is to come.

One Response to A Not Approvable Letter That Outlines What is Necessary for Approval

Certainly, whomever receives the first Complete Response Letter in mi-August will have the spotlight (even more so) on their FDA results. Imagine the investigators in Rockville all of whom have no desire to be the author of that inaugural letter!
“No, no, no, we need another few days to go over some final diligence. You go ahead & respond.” says one Investigator to another.
Here’s hoping that the actual result of that inevitable announcement gets as much attention as the groundbreaking format in which it is conveyed.

About This Blog

Eye on FDA is published by Mark Senak of FleishmanHillard's Washington, D.C. office. The thoughts and ideas in this blog and postings are strictly my own and are not screened by my employer. Everything posted on this blog is my personal opinion and does not necessarily represent the views of FleishmanHillard or its clients.